THE NITRIC-OXIDE DONOR ITF-1129 AUGMENTS SUBENDOCARDIAL BLOOD-FLOW DURING EXERCISE-INDUCED MYOCARDIAL-ISCHEMIA

The effect of the nitric oxide donor ITF 1129 and nitroglycerin (NTG) on myocardial blood flow was examined in dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left an terior descending coronary artery (LAD). Studies were performed during treadmill exercise in the presence of a coronary artery stenosis. The effects of ITF 1129 in doses of 3 and 10 mu g/kg/min i.v. were compar ed with NTG (2 mu g/kg/min i.v.). Neither ITF 1129 nor NTG caused sign ificant alteration of heart rate, arterial blood pressure, or left ven tricular systolic pressure. During partial inflation of the occluder t o decrease distal coronary pressure to 55 +/- 2 mm Hg, mean myocardial blood flow measured with microspheres was 0.72 +/- 0.14 ml/min/g in t he region perfused by the stenotic coronary artery compared with 2.93 +/- 0.40 ml/min/g in a normally perfused control region. With no chang e in distal coronary pressure, ITF 1129 increased mean myocardial bloo d flow in the stenosis perfused region to 1.15 +/- 0.24 ml/min/g (3 mu g/kg/min i.v.) and to 1.20 +/- 0.28 ml/min/g (10 mu g/kg/min i.v.), w hereas NTG (2 mu g/kg/min iv) increased blood flow to 1.16 +/- 0.22 ml /min/g (each p < 0.05). The increase in myocardial blood flow produced by ITF 1129 or NTG occurred principally in the deeper myocardial lave rs with no change in subepicardial flow. As a result, the subendocardi al/subepicardial blood flow ratio (ENDO/EPI) increased from 0.44 +/- 0 .09 during control stenosis to 0.85 +/- 0.13 after ITF 1129 (10 mu g/k g/min i.v.) and to 0.81 +/- 0.12 after NTG. Neither ITF 1129 nor NTG s ignificantly altered myocardial blood flow in the normally perfused co ntrol region. The effect of ITF 1129 and NTG on myocardial perfusion o ccurred without alterations of distal coronary pressure or left ventri cular diastolic pressure, indicating a primary effect on the intramura l coronary microvasculature.